Human cells produce many secretory proteins involved in cell growth and cell differentiation. TGF-beta superfamily proteins, which belong to the secretory proteins, have attracted a great deal of attention as a potential therapeutic agent because of their diverse biological activities [Massague, J., Annu. Rev. Cell Biol. 6: 597-641, 1988]. For example, TGF-beta 2, activin, inhibin, and bone morphogenetic proteins (BMP) are known as members of TGF-beta superfamily showing various biological activities including promotion and inhibition of cell growth, promotion and inhibition of cell differentiation, as well as promotion and inhibition of other cell functions. Thus these proteins have been investigated for using as medicine such as therapeutic agents for wound-healing, bone-related disease, anti-inflammation, and autoimmune diseases.
The carboxyl terminal of about 100 to 140 amino acid residues in TGF-beta superfamily proteins contains a characteristic amino acid sequence in which the position of seven cysteines is conserved. It is expected that there are many novel TGF-beta superfamily proteins playing an important role in a living cell.
Immunosuppressive agents such as steroid, cyclosporin, and FK506 have been used for therapy of autoimmune diseases or during an organ transplantation. However these compounds cause side effects, so that a new type of immunosuppressive agent has been desired.